Researchers uncover the enzyme that may be stifling your efforts to lose weight
Anyone who has struggled with the inconsistent results of dieting would be familiar with the way weight loss can plateau after a short period of time, signaling the body has altered its energy expenditure processes to burn less fat. University of California San Diego (UCSD) School of Medicine researchers have identified an enzyme that plays a key role in controlling these metabolic changes, suggesting we could tweak this pathway artificially to help our bodies burn fat more efficiently.
"Human bodies are very efficient at storing energy by repressing energy expenditure to conserve it for later when you need it," explains Alan Saltiel, from the UCSD research team. "This is nature's way of ensuring that you survive if a famine comes."
The study focused on an enzyme called TANK-binding kinase 1 (TBK1), previously known to play a major role in immune inflammatory responses but now discovered to fundamentally influence energy expenditure as well.
"There are two important observations that we have linked to slowing metabolism in obesity and fasting," says Saltiel of TKB1's role. "We've discovered two new feedback loops that are intertwined to self-regulate the system. Think of it like your home thermostat, which senses change in temperature to turn heat off and on."
AMP-activated protein kinase (AMPK) is one of the body's master regulators. It is an enzyme found in most cells and influences how a cell processes energy. When AMPK is activated, a cell will burn fat as its energy source, but the new research revealed that TBK1 can shut down the activity of AMPK, resulting in fat storage, and ultimately, obesity.
The research also revealed that when AMPK is activated through fasting it triggers the release of TBK1, which seems to act as a protective mechanism for the body to hold fat stores in the instance of famine. Of course, it is exactly this process which frustrates dieters when they are struggling to lose weight.
"Inhibiting TBK1 has the potential to restore energy balance in states of obesity by enhancing the ability to burn some fat," says Saltiel. "This is probably not the only pathway accounting for energy expenditure in fasting or obesity, but this information provides new insight into how we might develop drugs that inhibit TBK1 or other enzymes involved in metabolism."
This isn't the first research Saltiel and his team have undertaken examining the metabolic role of TBK1 and a drug target is already under investigation. For some years an asthma drug called amlexanox has been studied for its ability to inhibit TBK1, and a previous experiment showed that when administered to obese mice, it caused weight loss and increased the animals' sensitivity to insulin, helping improve their diabetes and fatty liver disease.
With amlexanox already proven safe for humans, and prescribed for over two decades, it offers an interesting clinical target for a weight loss drug. Saltiel does add that any drug that alters this metabolic pathway would only function successfully in association with other dietary alterations.
"I think you'll probably still have to do both: reduce energy intake through diet and increase energy expenditure by blocking this compensatory reduction in burning calories. We know that diets alone don't work and this is why."
The new study was published in the journal Cell.
Source: UC San Diego
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